Andrew W Johnson

Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp

We postulated that changes in cardiac high‐energy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Healthy volunteers (n=14) were studied immediately before, and within 4 d of return from, a 17‐d trek to Mt. Everest Base Camp (5300 m). 31P magnetic resonance (MR) spectroscopy was used to measure cardiac phosphocreatine (PCr)/ATP, and MR imaging and echocardiography were used to assess cardiac volumes, mass, and function. Immediately after returning from Mt. Everest, total body weight had fallen by 3% (P<0.05), but left ventricular mass, adjusted for changes in body surface area, had disproportionately decreased by 11% (P<0.05). Alterations in diastolic function were also observed, with a reduction in peak left ventricular filling rates and mitral inflow E/A, by 17% (P<0.05) and 24% (P<0.01), respectively, with no change in hydration status. Compared with pretrek, cardiac PCr/ATP ratio had decreased by 18% (P<0.01). Whether the abnormalities were even greater at altitude is unknown, but all had returned to pretrek levels after 6 mo. The alterations in cardiac morphology, function, and energetics are similar to findings in patients with chronic hypoxia. Thus, a decrease in cardiac PCr/ATP may be a universal response to periods of sustained low oxygen availability, underlying hypoxia‐induced cardiac dysfunction in healthy human heart and in patients with cardiopulmonary diseases.—Holloway, C. J., Montgomery, H. U., Murray, A. J., Cochlin, L. E., Codreanu, I. Hopwood, N., Johnson, A. W., Rider, O. J., Levett, D. Z. H., Tyler, D. J., Francis, J. M., Neubauer, S., Grocott, M. P. W., Clarke, K., for the Caudwell Xtreme Everest Research Group. Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp. FASEB J. 25, 792–796 (2011). www.fasebj.org

Oral Coenzyme Q10 supplementation does not prevent cardiac alterations during a high altitude trek to everest base cAMP.

Exposure to high altitude is associated with sustained, but reversible, changes in cardiac mass, diastolic function, and high-energy phosphate metabolism. Whilst the underlying mechanisms remain elusive, tissue hypoxia increases generation of reactive oxygen species (ROS), which can stabilize hypoxia-inducible factor (HIF) transcription factors, bringing about transcriptional changes that suppress oxidative phosphorylation and activate autophagy. We therefore investigated whether oral supplementation with an antioxidant, Coenzyme Q10, prevented the cardiac perturbations associated with altitude exposure. Twenty-three volunteers (10 male, 13 female, 46±3 years) were recruited from the 2009 Caudwell Xtreme Everest Research Treks and studied before, and within 48 h of return from, a 17-day trek to Everest Base Camp, with subjects receiving either no intervention (controls) or 300 mg Coenzyme Q10 per day throughout altitude exposure. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac morphology and function. Following altitude exposure, body mass fell by 3 kg in all subjects (p<0.001), associated with a loss of body fat and a fall in BMI. Post-trek, left ventricular mass had decreased by 11% in controls (p<0.05) and by 16% in Coenzyme Q10-treated subjects (p<0.001), whereas mitral inflow E/A had decreased by 18% in controls (p<0.05) and by 21% in Coenzyme Q10-treated subjects (p<0.05). Coenzyme Q10 supplementation did not, therefore, prevent the loss of left ventricular mass or change in diastolic function that occurred following a trek to Everest Base Camp.

Development and validation of a short 31P cardiac magnetic resonance spectroscopy protocol

Introduction Cardiac 31P-MRS is the only non-invasive in vivo technique for the determination of cardiac high energy phosphate metabolism. Changes in cardiac phosphocreatine to adenosine triphosphate ratios (PCr/ATP) occur in common cardiac pathologies and have diagnostic, prognostic and therapeutic utility. However, long acquisition times (20 minutes or more, depending on heart rate) required to achieve sufficient signal to noise ratios for reliable interpretation have limited the clinical utility of 31P-MRS studies in patients with severe cardiac disease.

Exercise training improves cardiac function, quality of life and exercise capacity in patients with dilated cardiomyopathy

Objective To determine the effects of short term exercise training on cardiac metabolism and function, during rest and exercise, in patients with dilated cardiomyopathy (DCM). Background Exercise training may play a beneficial role in patients with DCM, however the effects on cardiac function at rest and during exercise have not been defined. Methods Patients with DCM (n = 15, age 58 ± 2 years), stable on medical therapy, were studied before and after 8 weeks of training for 20 minutes, 5 times per week on a home exercise bike. Cardiac volumes and function were measured using MR at 3T during rest and leg exercise. High energy phosphate metabolism was measured as the ratio of phosphocreatine to ATP (PCr/ATP) by 31 Phosphorus magnetic resonance spectroscopy (MRS) at 3T. Quality of life scores were calculated using the Minnesota Heart Failure Questionnaire and 6 minute walk tests were used to determine exercise capacity. All assessments were repeated after the 8 week training period. Results At baseline assessment, the average left ventricular ejection fraction (LVEF) was 38 ± 3%, which did not increase with leg exercise. After the 8 weeks of home exercise there was a 6% improvement in resting LVEF to 44 ± 3% (Figure, p <0.01) and an 8% reduction in end systolic volumes (p <0.05). Exercise training led to a further 8% improvement in cardiac LVEF (p < 0.05) during leg exericse in the MR scanner. There was a moderate negative correlation between subjects baseline exercise per week and change in LVEF during the trial (Figure 1, r = -0.62, p <0.05). Patients also had an 8% improvement in 6 minute walk test and a 27% improvement in Minnesota heart failure questionnaire scores after the exercise training (both p <0.01). Patient with DCM had impaired resting PCr/ATP, with no change after exercise training.

Cardiac steatosis is associated with excess body weight in otherwise healthy adults

Background and aim Obesity confers an enormous burden of cardiovascular morbidity and mortality worldwide. Lipotoxicity has been implicated as a potential common pathway in myocyte dysfunction and ultimately apoptosis. Fat deposition in the peritoneum, the liver and around vascular structures has been linked to metabolic syndrome and subsequent cardiomyopathy. Therefore this study sought to determine the relationship between excess body fat and intracardiac lipids as assessed by 3T proton spectroscopy in women. Methods